Quaternary nitrogen containing polyvinyl alcohol polymers for use in skin conditioning, cosmetic and pharmaceutical formulations

ABSTRACT

Polyvinyl alcohol polymers having pendant cationic quaternary nitrogen containing groups provide for a film forming moisture barrier in skin conditioning lotions, ointments, cosmetic conditioning treatments and pharmaceutical formulations.

This application is a continuation-in-part of U.S. Ser. No. 06/540,041 filed Oct. 7, 1983 now abandoned and is directed to skin conditioning polymers which when applied to skin form thin films which aid in reducing moisture loss.

The invention relates in general to film forming polyvinyl alcohol polymer derivatives and specifically to those having ether-linked cationic quaternary nitrogen containing pendant groups. Of particular interest are polymers having a polyvinyl alcohol backbone or base chain having oxygen links on alternate carbon atoms with pendant substituent quaternary ammonium groups attached through ether linkages to the chain and spaced at random along the base chain. As a result of these quaternary ammonium groups in the polymer, thin film coatings on animal skin penetrate the outer layers of the skin to provide sufficient adhesive properties while remaining sufficiently elastomeric to avoid discomfort after drying. While the thin films act as a partially impenetrable barrier to prevent loss of moisture by evaporation they also behave as moisture retainers through the possible formation of hydrates at the quaternary ammonium sites and by inclusion of water molecules through hydrogen bonding on the hydrophilic polymer matrix. In general the compositions are made by treating readily available polyvinyl alcohol polymers with hydroxy reactive compounds containing quaternized ammonium groups linked thereto.

It is an object of the invention to provide for a quarternary nitrogen containing polyvinyl alcohol polymer base chain (having a number average molecular weight of at least 2,000 and preferably up to about 200,000 and higher when unmodified) and a random distribution of a multiplicity of pendant groups having the general formula:

    --R--N.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.-

which are linked directly to the polyvinyl alcohol polymer chain through ether (--OCHR₄ --) links on alternate carbon atoms of the base chain, and wherein

R is alkylene, substituted alkylene preferably hydroxyalkylene of formula weight ranging from 14 to about 3,000,

R₁, R₂, R₃ are alkyl or arylalkyl radicals having 1-22 carbon atoms which may be the same or different,

R₄ is H, alkyl, aryl or alkylaryl having 1-22 carbon atoms or another oxygen link to the base chain, and

A⁻ is an anion,

such that the total nitrogen content in the resin polymer ranges from 0.01%-7.0% by weight. Another object is to provide for a preferred process for the synthesis of such compositions. It is still another object to provide for aqueous solutions containing 0.1-30% by weight of these polymers which are useful in skin conditioning lotions, ointments, cosmetic and pharmaceutical formulations for application to hair, skin and nails. Another object is to provide for a film forming polymer which also performs as a dispersant for particulates in such formulations.

R in the above formula may be selected from alkyl groups such as methylene, ethylene, propylene, butylene, pentylene, hexylene, ethylhexylene, dodecylene, tetradecylene, hexadecylene, octadecylene, and substituted alkyl groups such as hydroxypropylene, hydroxybutylene, and their equivalents.

R₁, R₂, and R₃ may be selected from the alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl, decyl, dodecyl, tridecyl, tetradecyl, hexadecyl, octadecyl, octadecenyl, phenyl, and benzyl and their equivalents.

R₄ may be an alkyl, aryl or alkylaryl group having 1-22 carbon atoms to form a secondary ether link and preferably hydrogen. When R₄ is a --O-- link an acetal is formed with another carbon oxygen on the polyvinyl alcohol base chain.

A⁻ may be selected from a large number of anions such as chloride, bromide, iodide, hydroxide, lower alkylsulfate (1-6 carbon atoms), tetrafluoroborate, nitrate and perchlorate to name a few.

The quaternary nitrogen containing polyvinyl alcohol polymer compositions of the invention may be represented by a typical polymer segment having the following idealized structural formula:

    --[(--CH.sub.2 CHORN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.-)(--CH.sub.2 CHOH--).sub.m (CH.sub.2 CHORN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.-)].sub.n --

where

n=20-3000, and

m=0-600, and

R, R₁, R₂, R₃, and A⁻ are the same as described above.

Illustrative of the types of numerous pendant quaternary groups linked by oxygen as randomly distributed units in the polyvinyl alcohol base chain may be given as follows:

    --CH.sub.2 CH(OH)CH.sub.2 N.sup.+ (CH.sub.3).sub.3 Cl.sup.-( 1)

    --(CH.sub.2 CH[CH.sub.2 N.sup.+ (CH.sub.3).sub.3 Cl.sup.- ]O).sub.n CH.sub.2 CH(OH)CH.sub.2 N.sup.+ (CH.sub.3).sub.3 Cl.sup.- ( 2)

n=1-20

    (CH.sub.2).sub.n N.sup.+ (CH.sub.2 CH.sub.3).sub.3 Br.sup.-( 3)

    --CH.sub.2 CH(OH)CH.sub.2 N.sup.+ (CH.sub.3).sub.2 (CH.sub.2 Ph)Cl.sup.-( 4)

    --CH.sub.2 CH.sub.2 N.sup.+ (CH.sub.3)(CH.sub.2 CH.sub.3)(CH.sub.2 Ph)CH.sub.3 SO.sub.4.sup.-                                ( 5)

where Ph=phenyl or substituted phenyl

    >CH(CH.sub.2).sub.2 O(CH.sub.2).sub.2 N.sup.+ (CH.sub.3).sub.3 Cl.sup.-( 6)

    >CHCO.sub.2 (CH.sub.2).sub.2 N.sup.+ (CH.sub.3).sub.3 Cl.sup.-( 7)

    >CH(CH.sub.2).sub.2 N.sup.- (CH.sub.3).sub.3 Cl.sup.-      ( 8)

While the above structures serve to illustrate the types of pendant quaternary ammonium groups which can be added to the polyvinyl alcohol base chain it is apparent to one skilled in the art that many other arrangements of similar chemical structure can be easily incorporated. It has been found that each of the above types of groups used alone or in combination with one or more of the others as a substituent on the polyvinyl alcohol base chain yields the desired combination of products having useful moisture barrier properties especially when the nitrogen content of the final product ranges from 0.01%-7% and preferably 0.01-3% by weight. Depending on the type of radical attached to the nitrogen of the quaternary group the effective range of the nitrogen content could be even more specific. It has been found for example that when the R₁, R₂, R₃, in the above general formulas are all methyl radicals the effective nitrogen content may range from 0.1-3% by weight.

While many techniques have been employed in the art to add substituent quaternary groups to vary polymer charge four preferred methods for attaching the substituent groups to polyvinyl alcohol involve the reaction of the hydroxy groups of polyvinyl alcohol with an epoxy (oxirane) group, a halohydrin group in aqueous solution, a low molecular weight alkyl alcohol ester of the substituent in a dipolar aprotic solution or an aldehyde in either a dipolar aprotic solvent water or a two phase system in the presence of base catalyst or acid catalyst when appropriate.

While a number of methods may be utilized for the preparation of the PVA derivatives described in this invention, the use of non-aqueous solvents such as dimethyl formamide or similar polar materials is possible, but generally these solvents must be thoroughly removed from the final product. The use of aqueous solvents or mixed aqueous systems is preferable but, in this case, yields must be optimized because of competitive reactions of the quaternary ammonium compound with water as well as PVA hydroxyls in the presence of catalyst. Improved yields can be obtained by increasing the PVA concentration in water, adding the oxirane compound as a concentrate and reducing to a minimum the amount of base used to catalyze the addition reaction. Salt formed during the reaction is preferentially removed from the final product, since it may have a deleterious effect on the skin moisture barrier properties and its formulation. It has also been found that the pH of the derivatized PVA may affect the skin moisture barrier properties as well as the substantivity to skin. It is generally desirable to work in a pH range between 2-10 preferably from 5-9.

The product can be obtained in a dry form by precipitation, filtering, drying and grinding. The precipitation is accomplished by adding the reaction mixture to a nonsolvent such as acetone, methanol, ethanol and the like. The product also finds use in the form of the aqueous solution or suspension which can preferably be obtained by dialyzing the reaction mass to free it from salts and low molecular weight unreacted intermediates. To obtain a better understanding of the preparative techniques found to be most satisfactory attention is drawn to the following generalized and specific preparations which are intended to illustrate but not limit the invention and wherein all proportions mentioned are based on weight unless otherwise specified.

General Preparation I

A flask equipped with a water cooled condenser, mechanical stirrer and thermometer is charged with polyvinyl alcohol and distilled water. The polyvinyl alcohol (PVA) which is generally a commercially available product prepared by hydrolysis of polyvinyl acetate may have from 0 to 25% residual acetate groups, preferably from 2 to 15% and the number average molecular weight may range from 2,000 to 200,000 and higher and preferably from 25,000 to 150,000. The aqueous slurry is heated to 80°-90° C. and held for 1 hour or until the polyvinyl alcohol is completely dispersed or solvated. A catalytic amount of aqueous base such as alkali hydroxide such as sodium or potassium hydroxide is then added and the solution cooled to 40°-90° C. At this point 2,3-epoxypropyltrialkylammonium halide, either in aqueous solution or crystalline form, may be added incrementally or all at once. This reagent is typically used in 0.003-1.0 mol ratio preferably from 0.10-0.3 mol per mol of hydroxyl group on the polyvinyl alcohol base chain. The entire solution is then stirred for an additional period typically 4 hours at 60° C. after which the solid product may be recovered.

Recovery is accomplished by one of two general techniques. The solution can be poured into a polymer non-solvent to precipitate solid product from aqueous solution. Alternatively the solution may be dialyzed through a semiporous membrane and the purified aqueous polymer used as obtained or precipitated out.

The precipitation is preferably accomplished either in acetone or in methanol affording yields up to 90% or better by weight after drying. Depending on reaction conditions the precipitated products have a nitrogen content in the range of 0.01-7%.

In the purification by dialysis the reaction mixture is freed from all species below a certain molecular weight. Two methods may be used one a static and one dynamic. In the static method the reaction mixture is placed inside a commercial semiporous dialysis tube and the tubes are submerged in distilled water typically for periods of 12 to 48 hours. The contents of the tubes are then recovered and the product may be used as is. In the dynamic system a pressure pump is used to move water from the reaction mixture through a semi-pourous membrane. The water carries out any inorganics and low molecular weight organics. The resulting concentrated product stream is then collected.

General Preparation II

A flask equipped as described in General Preparation I is charged with polyvinyl alcohol and distilled water. The aqueous slurry is heated to 80°-90° C. and held for one hour or until the polymer is completely solvated, A catalytic amount of aqueous alkaline hydroxide such as sodium or potassium hydroxide is added and the pot cooled to 60°-65° C. At this point, (chlorohydroxypropyl)trimethylammonium halide, either in aqueous solution or crystalline form, is added either incrementally or all at once. This reagent is typically used in 0.003-1.0 mol ratio preferably from 0.10-0.5 mol per mol of hydroxyl group on the polyvinyl alcohol base chain. The entire solution is then stirred at 40°-90° C. for an additional period, typically four hours. The product is then recovered by one of the methods described in General Preparation I.

General Preparation III

In preparing quaternary ammonium groups linked to the polyvinyl alcohol base chain through acetalether links ##STR1## it is preferred to treat an aqueous solution of polyvinyl alcohol as previously described with a concentrated acid such as hydrochloric, sulfuric or acetic acid and thereafter add an apporpriate solution of a quaternary amine aldehyde at a temperature of 40°-90° C. and preferably about 60° C. An alternative two-step method involves first treating the acidified PVA solution with a haloaldehyde to form the haloacetal derivatized polymer followed by treatment with an appropriate amine solution to form quaternary amine linked at the halo-carbon by metathesis.

Solid polymer may be separated and recovered as described in General Preparation I.

General Preparation IV

A flask equipped as described in General Preparation I is charged with polyvinyl alcohol and distilled water. The aqueous slurry is heated to 80°-90° C. and held for one hour or until the polymer is completely dispersed or solvated. A catalytic amount of an acid such as sulfuric acid or aluminum hydrosilicate or any proton acid or Lewis acid is added and the pot cooled to 40°-90° C. At this point 2,3-epoxypropyltrialkylammonium halide may be added incrementally or all at once. This reagent is typically used in 0.003-1.0 mol ratio preferably from 0.1-0.3 mol per mol of hydroxyl group on the polyvinyl alcohol base chain. The entire solution is then stirred for an additional period typically 4 hours at 60° C. after which the solid product may be recovered by one of the methods described in General Preparation I.

The following examples and preparations serve to illustrate but not limit the invention. All proportions used refer to parts by weight unless otherwise specified.

Preparation A (Chlorohydroxypropyl)trimethylammonium chloride

A one-liter flask equipped with dropping funnel, mechanical stirrer, thermometer and condenser was charged with epichlorohydrin (95 grams, 1.02 mol) and placed in an isothermal bath at 18° C. Aqueous trimethylamine (238.7 grams, 25% by weight, 1.01 mol) was then added dropwise over a 3 hour period maintaining the temperature below 25° C. when the addition was complete the solution was allowed to stir overnight at ambient temperature.

EXAMPLE 1

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 --CH(OH)CH.sub.2 N(CH.sub.3).sub.3 Cl

A flask equipped as described in General Preparation I was charged with 44 grams polyvinyl alcohol (commercially available) having a molecular weight of 126,000 (98% hydrolyzed - 2% acetate) and 400 milliliters of distilled water. The resulting slurry was heated to 85° C. and held for 1 hour. The polymer dissolved completely to afford a pale yellow transparent solution. Potassium hydroxide (3.0 gram, 0.11 mol) in water (30 milliliters) was then added and the solution cooled to 60° C. Aqueous (chlorohydroxy propyl)trimethylammonium chloride (78 milliliters of 48% by weight aqueous solution prepared according to Preparation A), was then added all at once and the entire solution was heated to 60°-65° C. for 4 additional hours. The warm solution was poured with stirring into acetone (2.0 liters) and allowed to stand. 63.5 grams of colorless solid precipitate was collected by filtration shredded mechanically and dried under vacuum. The nitrogen content of the product was 2.15% by weight wherein the value for (m) in the above general formula segment is approximately 21.

PREPARATION B Crystalline 2,3-epoxypropyltrimethylammonium chloride

A one-liter flask equipped with gas sparger, mechanical stirrer, thermometer and an aqueous acid trap was charged with epichlorohydrin (55.2 grams, 6.0 mol) and placed in an isothermal bath at 19° C. Trimethylamine gas (119.5 grams, 2.0 mol) was then sparged into the epichlorohydrin over a period of 3 hours. The temperature was maintained below 23° C. The solution was stirred for an additional 30 minutes and the precipitate collected by filtration. The crystalline product was washed with diethylether and vacuum dried to afford 262.2 grams of 2,3-epoxypropyltrimethylammonium chloride.

EXAMPLE 2

    --RN.sup.+R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 CH(OH)CH.sub.2 N(CH.sub.3).sub.3 Cl

The procedure of Example 1 was repeated exactly except that pure crystalline 2,3-epoxypropyltrimethylammonium chloride (15.2 grams, 0.10 mol) was added in place of the aqueous solution. The mixture was then stirred for an additional 5.5 hours at 60° C. and recovered from acetone as described. The nitrogen content of the final product was 1.12% by weight wherein the value for (m) is approximately 28.

EXAMPLE 3

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 CH(OH)CH.sub.2 N(CH.sub.3).sub.3 Cl

The procedure of Example 1 was reproduced except that the amount of aqueous 2,3-epoxypropyltrimethylammonium chloride was 56.2 milliliters of 48% solution and the warm aqueous polymer was recovered by precipitation in methanol (2.0 liters). The solid collected was shredded mechanically dried under vacuum and milled to a fine powder. The yield was 49.9 grams and the nitrogen content was 0.22% by weight wherein the value for (m) in the general formula segment is approximately 282.

EXAMPLE 4

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 CH(OH)CH.sub.2 N(CH.sub.3).sub.3 Cl

The procedure of Example 3 was reproduced with the exception that the aqueous reaction mixture was cooled to ambient temperature and placed in a commercially available dialysis tube. The semi-pourous membrane in the dialysis tube retains all molecules with molecular weights greater than 8,000. The tubes were placed in water (4 liters) and allowed to stand. The bath water was changed ever 6-8 hours over a 36 hour period. The tubes were then recovered and the aqueous polymer solution inside was tested for moisture barrier properties.

EXAMPLE 5

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 CH(OH)CH.sub.2 N(CH.sub.3).sub.3 Cl

The procedure of Example 3 was reproduced with the exception that recovery was accomplished by precipitation from acetone (1.5 liters). The scale was slightly reduced to 38.0 grams polyvinyl alcohol and 49 milliliters of 48% aqueous epoxide solution. The yield was 63.5 grams and the nitrogen content was 2.63% by weight wherein the value for (m) in the general formula segment is approximately 15.

Preparation C Preparation of 2,3-epoxypropyltrimethylammonium bromide

A flask equipped with a sparger, mechanical stirrer, thermometer and efficiency condenser was charged with acetone (500 milliliters) at ambient temperature. Trimethylamine (58 grams, 0.98 mol) was charged into the solution. The pot was cooled to 10° C. and epibromohydrin (137 grams, 1.0 mol) was added dropwise over a 1 hour period. The resultant cloudy solution was allowed to slowly rise to ambient temperature and stand for 60 hours. Precipitate was collected by filtration washed with acetone (60 milliliters) and dried yielding a colorless crystalline product (179.4 grams, 94%).

EXAMPLE 6

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 CH(OH)CH.sub.2 N(CH.sub.3).sub.3 Br

A flask equipped as described in General Preparation I was charged with polyvinyl alcohol (44.0 grams), (98% hydrolyzed, number average molecular weight equals 126,000) and 500 milliliters water. The slurry was warmed to 70° C. and potassium hydroxide (3.0 grams) was added. The pot was stirred an additional 30 minutes and 2,3-epoxypropyltrimethylammonium bromide (49.0 grams, 0.25 moles) was added through a powder funnel. This solution was stirred for 16 hours at 80° C. The solution was then poured into acetone (1500 milliliters) and the precipitate was collected by filtration, shredded, washed and dried. The pale brown solid powder which resulted had a nitrogen content of 2.10% by weight wherein the value for (m) in the general formula segment is approximately 19.

EXAMPLE 7

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 CH(OH)CH.sub.2 N.sup.+ (CH.sub.3).sub.3 Cl

A flask equipped as described in General Preparation I was charged with polyvinyl alcohol (44.0 grams), (100% hydrolyzed, number average molecular weight equals 86,000), 200 milliliters distilled water and 3 grams potassium hydroxide. The pot was heated to 60° C. an aqueous (chlorohydroxypropyl)trimethylammonium chloride (320 milliliters, 48% aqueous solution as prepared in Preparation A) was added. Heating was continued for an additional 24 hours and recovery was accomplished by precipitation from acetone. After collection washing and drying the nitrogen content was 0.72% wherein the value for (m) in the general formula segment is approximately 80.

EXAMPLE 8

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 CH(OH)CH.sub.2 N.sup.+ (CH.sub.3).sub.3 Cl

A flask equipped as described in General Preparation I was charged with polyvinyl alcohol (88.0 grams), (98.5% hydrolyzed, having a molecular weight of 25,000) and 800 milliliters of water. The reaction was carried out exactly as described in Example 2 using crystalline 2,3-epoxypropyltrimethylammonium chloride (79.6 grams). Recovery was accomplished by precipitation in acetone. The nitrogen content was 1.01% by weight wherein the value for (m) in the general formula segment is approximately 84.

EXAMPLE 9

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =>CH(CH.sub.2).sub.2 O(CH.sub.2).sub.2 N.sup.+ (CH.sub.3).sub.3 Cl.sup.-

A 15% aqueous solution of PVA (100% hydrolyzed, MW=80,000) is acidified with concentrated sulfuric acid and thereafter reacted at 60° C. with a 10% aqueous solution of 3-oxopropyl-2-(N,N,N-trimethylammonium)ethyl ether chloride and stirred for 6 hours. The polymer is collected by precipitation in methanol.

EXAMPLE 10

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =>CH--CO.sub.2 (CH.sub.2).sub.2 N.sup.+ (CH.sub.3).sub.3 Cl.sup.-

According to the general procedure of Example 9, a 10% aqueous solution of PVA (90% Hydrolyzed, MW=125,000) is acidified with sulfuric acid and thereafter mixed with a 15% aqueous solution of N,N,N-trimethylammonium]ethyl glyoxylate chloride for 6 hours at 65° C. The polymer is collected by precipitation in methanol.

EXAMPLE 11

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 CH(OH)CH.sub.2 N.sup.+ (CH.sub.3).sub.3 Cl

Polyvinyl alcohol (44.0 g, MW=126,000, 98% hydrolyzed) was stirred in water (400 ml) and warmed to 85°-90° C. The solution was cooled to 80° C. and aqueous potassium hydroxide (5.6 g in 30 ml H₂ O) was added. This solution was cooled over 30 minutes to 60° C. and (3-chloro-2-hydroxypropyl)trimethylammonium chloride (18.8 g, 0.10 mol) was added all at once. The pH at this time was 7.3. The product was recovered by dialysis through a semi-porous membrane as previously described. The nitrogen content was 0.15% which corresponds to idealized formula with m=415.

EXAMPLE 12

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 CH(OH)CH.sub.2 N.sup.+ (CH.sub.3).sub.3 Cl

Polyvinyl alcohol (22.0 g), (MW=126,000, 98% hydrolyzed) was stirred in water (210 ml) and warmed to 85° C. over 45 minutes. Potassium hydroxide (1.5 g in 10 ml H₂ O) was then added and the solution cooled to 60° C. Crystalline 2,3-epoxypropyltrimethylammonium chloride (75.8 g, 0.50 mol) was added and the entire solution held at 60° C. for 4 hours. The product was then recovered by precipitation from acetone, filtration and drying to afford 102 grams of white powder. The nitrogen content was 5.96% or 88% of theoretical, and wherein (m) has a value of approximately 2.0.

EXAMPLE 13

    --RN.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.- =--CH.sub.2 CH(OH)CH.sub.2 N.sup.+ (CH.sub.3).sub.3 Cl

Polyvinyl alcohol (44.0 g), (MW=126,000, 98% hydrolyzed) was stirred in water (400 ml) and warmed to 85° C. over 30 minutes. The solution was cooled to 80° C. and Potassium hydroxide (3.0 g in 20 ml H₂ O) was added. The entire solution was cooled to 60° C. over 45 minutes and 2,3-epoxypropyltrimethylammonium chloride (37.9 g in 100 ml H₂ O) was added dropwise over 30 minutes. The solution was stirred at 60° C. for 3 additional hours and the product recovered by precipitation from acetone. The reaction afforded 50.4 grams of white solid with a nitrogen content of 2.92% or 71% of theoretical, and wherein (m) has a value of approximately 13.

EXAMPLE 14

A 500 ml. resin reactor fitted with an anchor agitator nitrogen sparge, reflux condenser and thermometer was charged with 125 g. PVA, 183 g. t-BuOH and 20.4 g. of sodium hydroxide (dissolved in 44.8 g. of distilled water). The nitrogen sparge was run at 100 ml/min. This slurry was agitated for an hour while bringing the temperature to 65° C. After an hour, 112.8 g. of a 60% solution of DOWQUAT™ 188 (3-chloro-2-hydroxypropyl)trimethyl ammonium chloride was added and reacted for two hours at 65° C. The reaction slurry was then filtered and the cake washed with MeOH and cold water. The cake was then dried in a vacuum oven. Analysis of the product showed that it contained 0.73% nitrogen which represents a 23.7% yield on the DOWQUAT™ 188 charged.

EXAMPLE 15

The reactor used in Example 14 was charged with 125 g. PVA, 312.5 g. MEK, and 17 g. of sodium hydroxide (dissolved in 62.5 g. of distilled water). After agitating for 0.5 hours and heating to 65° C., 94 g. of a 60% solution of DOWQUAT™ 188 was added. The slurry was reacted for two hours and washed and dried as above. The product contained 0.5% nitrogen for a 15.8% yield based on DOWQUAT™ 188 charged.

Moisture Barrier Test On Paper

While the modified polyvinyl alcohol polymers of the invention are best tested for retentivity, substantivity and moisture barrier film forming properties on living animal skin an indication of their effectiveness as a moisture barrier can be obtained by testing on filter paper. In the test results listed in the following Table 1 a 2.5 inch circle of number 1 Whatman filter paper was treated with aqueous solutions containing from 5-10% by weight of the modified polymer as described in the examples to obtain a polymer film deposit amounting to about 0.1 gram when dried at room temperature. The test is carried out by taking about 2 grams of aqueous solution of the modified polymer and dropping it over a water wet circle of filter paper from one side. The saturated paper is permitted to dry overnight at room temperature and weighed. Depending on the concentration of solution the procedure may be repeated until the weight pickup is about 0.1 gram so that each filter paper is treated with substantially an equal amount of polymer. The dry paper is sealed over the opening of a test cell containing 100 grams of water and permitted to stand for 100 hours in a constant humidity and temperature room at 70° F. at 40% relative humidity. The weight of water passing through the paper under these conditions is measured by weighing the amount of water remaining in the test cell. Each test employs a control cell containing the identical paper having no polymer treatment. Considering the weight loss through untreated paper as 100 the test results which are listed as percentage reduction in evaporation of water are calculated from the water remaining in the cell. The paper test results provide a rough indication of effectiveness as a moisture barrier for further testing on animal skin.

                  TABLE 1                                                          ______________________________________                                                           % Reduction                                                  Example           in Evaporation                                               ______________________________________                                         Control (unmodified PVA)                                                                         40-50                                                        1                 55                                                           2                 36                                                           3                 61                                                           4                 58                                                           5                 33                                                           6                 59                                                           7                 46                                                           8                 --                                                           ______________________________________                                    

In-vitro tests on animal skins having 1, 3 and 5 weight percent of the modified polyvinyl alcohol polymers of this invention indicate comparable results with regard to water vapor transmission on Neo-Natal Rat Stratum Corneum as shown in the results listed in Table 2.

                  TABLE 2                                                          ______________________________________                                         Water Vapor Transmission                                                       (5% polymer solution on neo-natal                                              rat stratum corneum)                                                           Sample        % Reduction                                                      ______________________________________                                         Control       66.7                                                             Example 1     55.6                                                             Example 7     77.8                                                             Example 8     55.6                                                             ______________________________________                                    

The effect of polymer coatings having 5% modified PVA polymers on the elasticity of pig skin is shown in Table 3.

                  TABLE 3                                                          ______________________________________                                         Elasticity of pig skin treated                                                 with 5% polymer solution                                                       Sample        Elasticity                                                       ______________________________________                                         Control       7.8 ± 2.6                                                     Example 1     8.8 ± 2.0                                                     Example 7     11.4 ± 2.0                                                    Example 8     -1.6 ± 0.8                                                    ______________________________________                                    

Compares skin elasticity (petroleum jelly produces maximum elasticity - approximately 28 units)

The use of unmodified polyvinyl alcohol polymer in film forming ointment bases and barrier creams for use in protecting the skin against the action of external irritants has met with only limited success (J.B. Ward and G. J. Sperandio, "American Perfumer and Cosmetics" Volume 79, pages 53-55 (1964)). Film forming creams are difficult to produce with polyvinyl alcohol because they are either very difficult to formulate because of their poor mixing characteristics or they form poor films. Lotions and creams made with polyvinyl alcohol in general lack elegance, that is, the in-vitro films made from ointments and lotions containing about 15% polyvinyl alcohol are either slow drying, become greasy and tacky and eventually leave a film which is hard and leathery. Furthermore, good PVA moisture barrier films usually are very hard to remove from the skin because they are difficult to remove with soap and water.

The problems associated with employing unmodified PVA in film forming bases are substantially overcome by the compositions of this invention in that they are easily dispersible in water are compatible with typical lotion formulations, and when applied to the surface of the skin, they dry quickly to form an elastic, smooth pellicle which retains its integrity over long periods of time and is easily removed with soap and water. Tests for pharmaceutical elegance is accomplished by applying typical moisture barrier lotion formulas to the back of the hand and making observations with respect to ease of application, feel on the skin, time of drying, durability of the film, ease of removal and a host of subjective factors. In most instances, the formulations evaluated do not adversely effect the film forming characteristics of the modified polyvinyl alcohol compositions of this invention. The aqueous moisture barrier compositions of the invention generally have a lotion consistency and may be in the form of oil-in-water or water-in-oil emulsions with the former being preferred because of their more pleasing cosmetic properties. The lotions are preferably made by first preparing the oil phase then preparing the water phase and thereafter adding the water phase to the oil phase. Usually the aqueous phase is heated to a temperature of about 70° to about 80° C. and then added slowly with stirring to the oil phase which is heated to about the same temperature.

The oil phase components may contain a variety of materials including emulsifiers, emollients, oils, waxes, perfumes, lanolins, polyalkylenes, stearols and the like.

Water phase components may contain many different materials which include humectants, modified PVA moisture barrier components of the invention, proteins and polypeptides, preservatives, alkaline agents, thickening agents, perfumes, stabilizers and antiseptics.

The lotions and ointments in pharmaceutical compositions of the invention contain as an essential ingredient may contain 0.5-99.5 and usually from 0.1-15% by weight, but preferably from 0.5-5% by weight of the above described modified polyvinyl alcohol polymers of the invention. They may be added as aqueous dispersions containing 0.1-30% by weight of modified PVA or as dry powder.

The lotions may contain an emulsifier in an amount of from about 0.05 to about 8% and preferably from about 0.25 to about 5% to emulsify the oil components. Typical emulsifiers are selected from the group consisting of polyethoxylated fatty acids having less than about 30 mols of ethylene oxide per mol of fatty acid, ethyoxylated esters, unethoxylated sugar esters, polyoxyethylene fatty ether phosphates, fatty acid amides, phospholipids, polypropoxylated fatty ethers, acyllactates, polyethoxylated polyoxypropylene glycols, polypropoxylated polyoxyethylene glycols, polyoxyethylene, polyoxypropylene ethylene diamines, soaps and mixtures thereof.

Examples of such emulsifiers include polyoxyethylene (8) stearate, myristyl ethoxy (3) myristate, myristyl ethoxy (3) palmitate, methyl glucose sesquistearate, sucrose distearate, sucrose laurate, sorbitan monolaurate, polyoxyethylene (3) oleyl ether phosphate, polyoxyethylene (10) oleyl ether phosphate, lauric diethenyl amide, stearic monoethyl amide, lecithin, lanoline alcohol propoxylates, sodium stearoyl-2-lactate, calcium stearoyl-2-lactate, and the Pluoronics® offered by BASF Wyandotte. Soaps such as alkaline metal or triethanolamine salts of long chain fatty acids which include sodium stearate, triethanolamine stearate and similar salts of lanolin fatty acids. A preferred emulsifier is polyoxyethylene (21) stearyl ether.

The lotion formulations may contain an emollient material in an amount ranging from 0.2 to 25% and more often 1 to 8% by weight. One function of the emollient is to ensure that the modified polyvinyl alcohol polymer is classified sufficiently to allow it to be in a film-like state on the surface of the skin. Typical emollients are selected from the group consisting of fatty alcohols, esters having fewer than about 24 carbon atoms (for example, isopropylpalmitate), branch chain esters having greater than about 24 total carbon atoms (for example, cetearyl octonate), squalane, liquid or solid paraffins, mixtures of fatty acids and squalane, mixtures of fatty acids and liquid or solid paraffins and mixtures thereof. Typical alcohols and fatty acids which are useful include those having from 12 to 22 carbon atoms such as cetyl alcohol, myristyl alcohol, stearyl alcohol, stearic acid and palmitic acid. Paraffins include, for example, mineral oil, petrolatum and paraffin wax.

The lotions and ointments are particularly stable and effective when adjusted to a pH of 6-8.

The following formulations will serve to demonstrate but not limit the formulations containing the modified polyvinyl alcohol film forming moisture barrier polymer of the invention. Typical lotions contain 0.1-5.0% of the above described modified PVA polymers, 2-5% of a fatty alcohol, and 2-5% emulsifier in an aqueous emulsion.

EXAMPLE A

A portion of the aqueous solution prepared according to Example 4 containing 0.5 grams of modified PVA polymer was diluted with water and added to an aqueous solution containing 2.4 grams cetyl alcohol, 1.6 grams stearyl alcohol and 3.0 grams of polyoxyethylene (21) stearyl ether (BRIJ® 721 surfactant by ICI Americas Inc.). Additional water was added to bring the water concentration to 92.5%. After stirring for about five minutes at 75° C. the emulsion is permitted to cool to room temperature and stored. The lotion was tested subjectively for cosmetic elegance by applying the product to the back of the hand and arm. It was determined to have smooth, silky feel, drying time of less than 15 minutes and a film durability in excess of two days. Residual films and lotions are easily removed from the skin with soap and water.

As mentioned above the polymers of the invention had advantageous cosmetic properties that permit them to be used in preparing cosmetic formulations either as ready to use compositions or concentrates which have to be diluted before use. Therefore, the cosmetic formula may contain the modified polyvinyl alcohol polymers in concentrations ranging from 0.01-15% by weight. The solution of these polymers are particularly useful when they are applied to hair, either alone or with other active substances during a treatment such as shampooing, dyeing, setting, blow drying, permanent waving, etc. They may improve notably the quality of the hair. When employed in hair treatment they facilitate untangling of wet hair and do not remain on dry hair as a sticky residue. In some instances they are expected to give dry hair additional life, a soft feel, a glossy appearance and resistance to tangling.

Hair treating formulations containing dilute aqueous, alcohol or dilute alcohol solutions of the modified polyvinyl alcohol polymer can be employed. Furthermore, they may be employed as creams, lotions, gels or as aerosol sprays. They may be used in combination with perfumes, dyes, preserving agents, sequestering agents, thickening agents, emulsifying agents, etc.

EXAMPLE B

A typical hair rinse formulation containing 5 grams of the modified polymer of Example 8, 7 grams cetyl alcohol, 3 grams of a linear polyoxyethylenated C₁₀ -C₁₈ fatty alcohol, 2 grams of a casein derivative, 0.5 grams tetradecyltrimethylammonium chloride and 82.5 grams of water and a minor amount of hair dye can be used to treat hair having improved looks and anti-static properties.

EXAMPLE C

A typical oxidation hair dye solution containing a 2.5 gram of the modified polymer of Example 7, 10 grams benzyl alcohol, 20 grams oleic acid, 3 grams polyoxyethylene (30), oleo cetyl alcohol, 7 grams oleic diethanolamide, 7.5 grams 2 octyldodecanol, 2.5 grams triethanolamine lauric sulfate, 10 grams ethanol, 18 millileters aqueous ammonium, 1 gram n,n-bis(2-hydroxyethanol)paraphenylenediamine, 0.4 grams resorcin, 0.15 grams m-aminophenol, 0.4 grams alphanaphthol, 0.1 grams hydroquinone, 0.24 grams ethylene diamine tetracetic acid, 1 milliliter sodium bisulfite, and water sufficient to make 100 grams is a typical ammonia oil composition for use as an oxidation hair dye when 130 grams of the solution is mixed with 30 grams of hydrogen peroxide bleach. After hair is treated with the material and allowed to stand for 30-40 minutes and thereafter rerinsed the hair is expected to untangle easily and have a silky touch.

The modified polyvinyl alcohol compositions of the invention may be employed to improve the elegance and stability of personal care products such as liquid and bar soaps, shaving creams, bath products, antiperspirants, sunscreens, cleansing creams and as a suspending agents for insoluble pigments and pharmaceutical actives. Improvement is generally realized when from 0.5-5% by weight of the compositions of this invention are employed in conventional formulations as hereinafter exemplified.

EXAMPLE D

    ______________________________________                                         Roll-On Antiperspirant                                                         Ingredient           % W/W                                                     ______________________________________                                         Example 3            4.0                                                       polyoxyethylene (21) stearylether                                                                   0.76                                                      polyoxyehtylene (2) stearylether                                                                    3.24                                                      water (deionized)    34.76                                                     Dowicil 200 ®, Dow Chemical                                                                     0.1                                                       Al Zr tetrachlorohydrex-Gly,                                                                        57.14                                                     Rezol 36G, Reheis                                                              ______________________________________                                    

EXAMPLE E

    ______________________________________                                         Aerosol Shave Cream                                                            Ingredient           % W/W                                                     ______________________________________                                         Example 3            5.0                                                       Cetyl alcohol        4.3                                                       polyoxyethylene (21) stearylether                                                                   2.2                                                       sorbic acid          .17                                                       water                74.9                                                      fragrance            .08                                                       water                13.35                                                     ______________________________________                                    

EXAMPLE F

    ______________________________________                                         Oil-in-Water Sunscreen Lotion                                                  Ingredient             W/W %                                                   ______________________________________                                         mineral oil            18.8                                                    cetyl alcohol          5.0                                                     Arlocel 60 ® emulsifier                                                                           2.5                                                     Tween 60 ® emulsifier                                                                             7.5                                                     Amyl para-dimethylaminobenzoic acid                                                                   1.2                                                     Example 4              2.0                                                     water                  63.0                                                    Preservative q.s.                                                              ______________________________________                                    

EXAMPLE G

    ______________________________________                                         Water-in-Oil Pigmented Makeup                                                  Ingredient         W/W %                                                       ______________________________________                                         Mineral Oil        10                                                          Beeswax            1.5                                                         Cevesin wax        1.0                                                         Arlacel 186 ® emulsifier                                                                      3.2                                                         Sorbo ® sorbitol                                                                              28.8                                                        TiO.sub.2 and other pigments                                                                      20.0                                                        water              33.5                                                        Example 6          2.0                                                         ______________________________________                                    

EXAMPLE H

    ______________________________________                                         Calamine Lotion                                                                ______________________________________                                         Calamine               80     gms                                              Zinc Oxide             80     gms                                              glycerine              20     mls                                              bentonite magma        250    mls                                              calcium hydroxide      950    mls                                              (concentrated aqueous sol.)                                                    Example 1              50     gms                                              ______________________________________                                     

What is claimed is:
 1. A quaternary nitrogen modified polyvinyl alcohol film forming polymer useful in skin conditioning, cosmetic, and pharmaceutical formulation which consists essentially of a preformed polyvinyl alcohol base chain with oxygen links on alternate carbon atoms and a molecular weight ranging from 2,000-200,000 having pendant groups of the general formula: --R--N⁺ R₁ R₂ R₃ A⁻ which are linked directly to the polyvinyl alcohol chain through ether (--OCHR₄ --) links, wherein R is selected from the group consisting of an alkylene, a hydroxy alkylene and an etheralkylene;R₁, R₂ and R₃ are selected from the group consisting of alkyl or arylalkyl radicals having 1-20 carbon atoms, R₄ is H, alkyl, aryl or arylalkyl having 1-22 carbon atoms or another oxygen link to the base chain, and A⁻, is an anion said polymers having a total nitrogen content ranging from 0.01-3% by weight.
 2. A composition of claim 1 wherein said polyvinyl alcohol base chain has a number average molecular weight of 25,000-150,000.
 3. A composition of claim 1 wherein R is a radical selected from the group consisting of --CH₂ --CHOH--CH₂ --and

    --[(CH.sub.2 CH(CH.sub.2 N.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.-)O].sub.n CH.sub.2 CH(OH)CH.sub.2 --

wherein R₁, R₂ and R₃ is alkyl and arylalkyl radicals having 1-22 carbon atoms, and A⁻ is halide or lower alkylsulfate ion and n=1-22.
 4. A composition of claim 1 wherein said pendant group is acetal linked having a general formula ##STR2##
 5. A composition of claim 1 wherein R₁, R₂ and R₃ are selected from the group consisting of ##STR3## and --CH₂ Ph where Ph is phenyl.
 6. A composition of claim 1 wherein R₁, R₂ and R₃ are selected from the group consisting of ##STR4## where Ph is phenyl.
 7. An aqueous dispersion comprising from 0.1-30% by weight of a composition of claim
 1. 8. A composition of claim 1 wherein R₁, R₂ and R₃ are methyl groups and the nitrogen content ranges from 0.1 to 3% by weight.
 9. A composition of claim 1 prepared by the steps of (a) reacting equimolar quantities of epichlorohydrin with aqueous trimethylamine at temperatures below 25° C. and (b) reacting at 40°-90° C. the aqueous product of step (a) with an aqueous dispersion of polyvinyl alcohol having a number average molecular weight of at least 2,000 containing catalytic quantities of base.
 10. A composition of claim 1 when made by reacting (chlorohydroxypropyl)trialkylammonium chloride in aqueous solution or crystalline form with an aqueous solution of polyvinyl alcohol having a number average molecular weight of at least 2,000, said solution containing catalytic quantities of potassium hydroxide, and maintaining the resulting reaction mixture at 40°-90° C.
 11. A composition of claim 1 when made by reacting an aqueous dispersion of polyvinyl alcohol polymer having a number average molecular weight of at least 2,000 with an aqueous solution of 2,3-epoxypropyl trialkylammonium halide, said reaction being carried out at a temperature of 40°-90° C. in the presence of a catalytic amount of base in amounts wherein the mol ratio of said ammonium halide to each mol of hydroxyl group on the polyvinyl alcohol polymer ranges from 0.003-1.
 12. A composition of claim 1 when made by reacting an aqueous dispersion of polyvinyl alcohol polymer having a number average molecular weight of at least 2,000 with an aqueous solution of 2,3-epoxypropyltrialkylammonium halide at a temperature of 40°-90° C. in the presence of a catalytic amount of acid in amounts wherein the mol ratio of said ammonium halide to each mol of hydroxyl group on the polyvinyl alcohol polymer ranges from 0.003-1.
 13. A composition of claim 1 when made by reacting 2,3-epoxypropyltrimethylammonium chloride in aqueous solution or crystalline form with an aqueous dispersion of polyvinyl alcohol having number average molecular weight ranging from 2,000-200,000 and a random distribution of oxygen linked pendant groups having a general formula:

    --R--N.sup.+ R.sub.1 R.sub.2 R.sub.3 A.sup.-

wherein R is selected from the group consisting of an alkylene, a hydroxy substituted alkylene, radical.
 14. A composition of claim 1 when made by reacting 2,3-epoxypropyltrimethylammonium chloride in aqueous solution with an aqueous dispersion of polyvinyl alcohol having a number average molecular weight of at least 2,000, said reaction being carried out at a temperature of 40°-90° C. in the presence of a catalytic amount of base in amounts wherein the mol ratio of said ammonium halide to each mol of hydroxyl group on the polyvinyl alcohol polymer ranges from 0.003-1.
 15. A composition of claim 1 when prepared by reacting polyvinyl alcohol having a number average molecular weight of 2000-200,000 with an aldehyde derivative of a quaternary ammonium compound in the presence of acid catalyst at a temperature of 40°-90° C. in aqueous solution.
 16. A composition of claim 15 wherein said aldehyde is selected from the group consisting of 3-oxopropyl-2-(N,N,N-trimethylammonium)ethyl ether halide, 2-[N,N,N-Trimethyl ammonium]ethyl glyoxylate halide, and 3-[N,N,N,-Trimethyl ammonium]propanal halide.
 17. A composition of claim 1 which is separated from an aqueous reaction mixture by precipitation through the addition of a nonsolvent selected from the group consisting of acetone and methanol.
 18. A composition of claim 1 which is purified by dialysis or ultrafiltration. 